Pharmacokinetics Flashcards
(26 cards)
What is pharmacokinetics
What the body does to the drug
1. Absorption
2. Distribution
3. Metabolism
4. Excretion
Can you describe absorption?
○ Absorption of a drug = absorption into the blood
○ Absorption depends on the form of a drug and site of admin
○ It is influenced by the different transport mechanisms across the membrane
Physiological factors affecting absorption?
- Blood flow
- Surface area (Greater surface area, greater absorption)
- Gastric motility
- Other substances (food=delayed stomach emptying) can lead to inhibited or increased absorption
Physio-chemical factors affecting absorption?
- Acid base status (the balance of water solubility and lipid solubility)
- Ionisation (uncharger and unionised=increases absorption
Explain passive diffusion?
(Gap in fence)
○ Depenent on lipid solubility of the drug
○ Drugs have to be lipid soluble to pass the membrane
○ Drugs flow from an area of high to low concentration
Explain facilitated passive diffusion?
(Larger molecules=walk through gate)
○ Passive movement of molecules across the cell membrane via the aid of membrane protein
○ Require no energy
○ Not lipid soluble
Explain active transport?
(Voltage operated gate)
○ Active transport uses energy to move molecules from low to high concentration.
○ needs energy
○ uses carrier proteins called protein pumps
Define distribution?
○ Distribution=Distribution from the blood to the peripheral tissues
○ As soon as a drug enters the blood it will start to be distributed throughout the body
Explain first pass metabolism?
○ Breaks down drug so not all of it goes to distribution
○ Drug absorbed through intestine
–> to hepatic portal vein
–> to the liver
–> Liver metabolises either partially or fully before entering systemic circulation
–> affects bioavailability
Factors affecting distribution?
- Blood circulation
- Degree if the drugs binding to plasma proteins
- The water and lipid solubility of the drug
- Distribution barriers
Better blood flow=better Distribution
Drug binding to plasma proteins
○ Drugs will bind proteins
○ Different proteins will have different affinity to bind different drugs
○ only free drugs are active
○ protein bounds drugs are inert
○ some drugs displace others from their binding sites
Physiological factors affecting protein binding?
- Burns
- Malnutrition
- Liber disease
(All reduced levels of plasma albumin)
–> Less proteins in the blood means less protein binding & more free drug –> leading to over dose, side effects, adverse effects
Define metabolism?
○ A process whereby the chemical structure of a drug is changed
○ aim = make drug more water soluble
What are the 2 phases of metabolism?
Phase 1 = where the drug is modified to a reactive metabolite
1. Oxidation
2. Reduction
3. Hydrolysis
Phase 2 = fuses together with another compound to form a water soluble conjugated complex
Enzyme process/interactions
○ The metabolic activity of the liver is carried out by the enzymatic process
○ Can be affected by age, disease, drug interaction
○ Enzyme induction = drugs metabolism faster + drug concentration decreased
& ○ Enzyme inhibition = drugs metabolised slower + drug concentration increased
Define excretion?
○ The kidneys = most important organ for elimination by excretion
○ water-soluble drugs will follow the flow of filtration through the rest of the nephron and be excreted in the urine
○ Lipid-soluble drugs are subject to reabsorption
–> to the blood, through the liver again to be metabolised to water-soluble metabolites
The 5 R’s of drugs administration
- Right patient
- Right drug
- Right dose
- Right route
- Right time/frequency
Nature of the drug
- Available in suitable forms
- Administered by appropriate route
- Absorbed
- Distributed
- Metabolised
- Excreted
Define therapeutic window/narrow therapeutic index?
The intention is to achieve the therapeutic effect quickly, for an appropriate duration of action and without side effects
Define time to onset?
Time it takes for a drug to reach its site of action at a concentration necessary for it to work
Define half-life?
The time it takes for the peak concentration of a drug in the plasma to reduce d by half
Define duration of effect?
The time interval where the concentration of drug at its site of action is above its therapeutic concentration
○ may be prolonged in elderly or people with poor liver or kidney function
Define bioavailability?
○ The percentage of drug administered that reaches the systematic circulation after absorption
Define steady state ?
○ When the drug going into the body = the drug going out
○ usually achieved after 4-5 half lives
